This invention relates to the most stable crystalline polymorph Form I of (xe2x88x92)-4-[4-[4-[4-[[(2R-cis)-5-(2,4-difluorophenyl)tetrahydro-5-(1H-1,2,4-triazol-1-ylmethyl)furan-3-yl]methoxy]phenyl]-1-piperazinyl]phenyl-2,4-dihydro-2-[(S)-1-ethyl-2(S)-hydroxylpropyl]-3H-1,2,4-triazol-3-one represented by the formula I (hereinafter xe2x80x9cthe compound of formula Ixe2x80x9d) 
pharmaceutical compositions containing such polymorph and methods of using such polymorph to treat fungal infections in mammals.
International Publication Numbers WO/95/17407(published Jun. 29, 1995 and WO 96/38443(published Dec. 5, 1996) disclose methods of making the compound of formula I and using it to treat antifungal infections in mammals. These International Patent Publications do not disclose or refer to, or even suggest the possible existence of a crystalline polymorph of the compound of formula I; the synthetic procedures disclosed therein produce the compound of formula I as an amorphous solid.
To prepare pharmaceutical compositions containing the compound of formula I for administration to mammals in accordance with exacting health registration requirements of the U.S. and international health registration authorities, e.g. the FDA""s Good Manufacturing Practices(xe2x80x9cGMPxe2x80x9d)requirements, there is a need to produce the compound of formula I in as pure a form as possible, especially a form having constant physical properties.
We have discovered that the compound of formula I can exist in the form of three crystalline polymorphs, each having distinctly different from each other and from the amorphous form in their physico-chemical data, their physical properties and their methods of preparation. These three novel crystalline polymorph forms described in this specification are hereinafter referreds to as form I, form II and Form III. Of the three forms. Form I is the most stable.
Accordingly, this invention provides a crystalline polymorph Form I of (xe2x88x92)-4-[4-[4-[4-[[(2R-cis)-5-(2,4-difluorophenyl)tetrahydro-5-(1H-1,2,4triazol-1-ylmethyl)furan-3-yl]methoxy]phenyl]-1-piperazinyl]phenyl-2,4-dihydro-2-[(S)-1-ethyl-2(S)-hydroxylpropyl]-3H-1,2,4-triazol-3-one represented by formula I 
and characterized by the following x-ray powder diffraction pattern expressed in terms of xe2x80x9cdxe2x80x9d spacing and relative intensities(xe2x80x9cRIxe2x80x9d):
This invention also provides a crystalline polymorph Form I of(xe2x88x92)-4-[4-[4-[4-[[(2R-cis)-5-(2,4-difluorophenyl)tetrahydro-5-(1H-1,2,4-triazol-1-ylmethyl)furan-3-yl]methoxy]phenyl]-1-piperazinyl]phenyl-2,4-dihydro-2-[(S)-1-ethyl-2(S)-hydroxylpropyl]-3H-1,2,4-triazol-3-one characterized by the following x-ray powder diffraction pattern (Table 1)expressed in terms of xe2x80x9cdxe2x80x9d spacings and relative intensities (xe2x80x9cRIxe2x80x9d)(S=strong, M=medium, W=weak, V=very , D=diffuse and VWD, for example=very weak diffuse):
This invention further provides pharmaceutical composition containing the crystalline polymorph of Forms I,and methods of treating and/or preventing fungal infections using such a crystalline polymorph.